Synergistic interactions between Ca2+ entries through L-type Ca2+ channels and Na+-Ca2+ exchanger in normal and failing rat heart.

We used confocal Ca2+ imaging and the patch-clamp technique to investigate the interplay between Ca2+ entries through L-type Ca2+ channels (LCCs) and reverse-mode Na+-Ca2+ exchange (NCX) in activating Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) in cardiac myocytes from normal and failing rat hearts. In normal myocytes exposed to N(6),2'-O-dibutyryl adenosine-3',5'-cyclic monophosphate (db-cAMP, membrane-permeable form of cAMP), the bell-shaped voltage dependence of cytosolic Ca2+ transients was dramatically broadened due to activation of SR Ca2+ release at high membrane potentials (30-120 mV). This broadening of Ca2+-transient voltage dependence could be prevented by KB-R7943, an inhibitor of the reverse-mode NCX.

Lack of central effects of peripherally administered adenosine A(1) agonists on synaptic transmission in the rat hippocampus.

Peripheral administration of adenosine A(1) receptor selective agonists is generally thought to protect the hippocampus against ischemic damage via central actions. We examined the effects of two peripherally administered A(1) agonists, cyclohexyladenosine (CHA) and adenosine amine congener (ADAC), on synaptic transmission in the hippocampus and on indices of cardiovascular function. We conclude that the permeability of these agonists is not sufficient to result in concentrations necessary to activate central adenosine A(1) receptors within the hippocampus.